Patel Vivek P, Chu Charleen T
Center for Neuroscience at the University of Pittsburgh, PA, USA.
Int J Clin Exp Pathol. 2011 Mar;4(3):215-29. Epub 2011 Feb 28.
Trafficking of transcription factors between the cytoplasm and the nucleus is an essential aspect of signal transduction, which is particularly challenging in neurons due to their highly polarized structure. Disruption in the subcellular localization of many proteins, including transcription factors, is observed in affected neurons of human neurodegenerative diseases. In these diseases, there is also growing evidence supporting alterations in nuclear transport as potential mechanisms underlying the observed mislocalization of proteins. Oxidative stress, which plays a key pathogenic role in these diseases, has also been associated with significant alterations in nuclear transport. After providing an overview of the major nuclear import and export pathways and discussing the impact of oxidative injury on nuclear trafficking of proteins, this review synthesizes emerging evidence for altered nuclear transport as a possible mechanism in the pathogenesis of neurodegenerative diseases. Potential strategies to overcome such deficits are also discussed.
转录因子在细胞质和细胞核之间的运输是信号转导的一个重要方面，由于神经元具有高度极化的结构，这在神经元中尤其具有挑战性。在人类神经退行性疾病的受影响神经元中，观察到包括转录因子在内的许多蛋白质的亚细胞定位紊乱。在这些疾病中，也有越来越多的证据支持核运输改变是观察到的蛋白质错误定位的潜在机制。氧化应激在这些疾病中起关键的致病作用，也与核运输的显著改变有关。在概述主要的核输入和输出途径并讨论氧化损伤对蛋白质核运输的影响之后，本综述综合了新出现的证据，表明核运输改变可能是神经退行性疾病发病机制中的一种机制。还讨论了克服此类缺陷的潜在策略。
